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Biomedical subjects

R S Geha

Publications and source records attributed to R S Geha.

At least 289 records · Page 16Linked to original sources
PubMed1978

Antigen-specific helper factor in man.

Supernates of tetanus toxoid (TT) antigen-stimulated human T cells were studied for the presence of an antigen-specific T-cell helper factor (ASF). Supernates were circulated over an immunosorbent column consisting of insolubilized TT antigen. The material which bound to the column was eluted with 3 M NaCNS and was shown to contain a factor which in the presence of TT-induced specific IgG anti-TT antibody synthesis in autologous B cells without causing readily detectable proliferation. ASF activity was partially inhibited by antisera directed against the B-cell alloantigens of the ASF donor. Immunosorbent columns containing such antisera removed ASF activity. Immunosorbent columns containing antisera to human immunoglobulin heavy chain determinants did not remove ASF activity; whereas immunosorbent columns containing rabbit idiotypic antiserum directed against anti-TT antibodies completely removed ASF activity. ASF was destroyed by treatment with proteolytic enzymes; its molecular weight was estimated by Sephadex G-100 gel column chromatography to be between 25,000 and 75,000 daltons.

Antibody Formation↗
PubMed1977

The specificity of T-cell helper factor in man.

Supernates of human T cells stimulated with TT antigen contain a factor that induces mitogenesis and immunoglobulin synthesis in autologous as well as allogeneic B cells. A fraction of the IgG produced has specificity against TT. The T-cell-derived LMF-TT eluted after albumin on Sephadex G 200 and did not contain immunoglobulin heavy chain determinants. LMF-TT was active on B cells from TT immune as well as TT- nonimmune individuals but in the latter instance the IgG secreted had no specificity against TT. B cells incubated with LMF-TT in the presence of a second antigen (DT) made IgG with specifity to that antigen provided the B-cell donor was immune to that second antigen. LMF-TT-containing supernates were depleted of TT antigen by Sephadex G 200 chromatography followed by passage over anti-TT immunosorbent columns. The antigen-free supernates were able to induce mitogenesis and IgG synthesis in B cells but the IgG produced failed to exhibit specificity against TT unless the TT antigen was readded to the B-cell cultures. The optimal concentration of LMF-TT (50 percent) inducing B-cell mitogenesis was different from the optimal concentration (20 percent) causing IgG synthesis by B cells. At low LMF concentrations (less than or equal 10 percent) addition of a second antigen to which the cell donor was immune caused an increase in the degree of B-cell mitogenesis. Submitogenic concentrations of LMF-TT (less than or equal to 5 percent) were still capable of inducingimmunoglobulin synthesis in B cells At these low concentrations of LMF-TT the proportion of anti-TT IgG over total IgG increased sharply. B cells from TT immune donors were separated on TT immunosorbent columns. Cells that bound to the column were more sensitive to the mitogenic and IgG synthetic effects of LMF-TT than unfractionated B cells. Thus, LMF is a nonspecific human T-cell helper factor which behaves like a polyclonal B-cell activator. However, in the presence of specific antigen (TT) the antigen-specific B cell is preferentially triggered by LMF. The experimental design of the present study does not rule out the additional presence of an antigen-specific helper factor in the supernates of TT-stimulated human T cells.

Antibody Formation↗
PubMed1977

Circulating immune complexes and activation of the complement sequence in acute allergic bronchopulmonary aspergillosis.

A 13-yr-old asthmatic girl with allergic bronchopulmonary aspergillosis (ABPA) exhibited eosinophilia, IgE hypergammaglobulinemia, serum precipitins to Aspergillus, a dual skin reaction to Aspergillus fumigatus, and positive, lymphocyte transformation in vitro in response to stimulation with Aspergillus fumigatus antigen. The acute phase of the disease was characterized by an increase in blood eosinophilia, a rise in serum IgE, circulating immune complexes, and evidence of activation of the complement system through the classical pathway.

Adolescent↗
PubMed1977

Genetics of cell-mediated lympholysis in man.

Cell-mediated lympholysis (CML) was studied in a family containing two siblings in who genetic recombinaiton had occurred in the HLA comples. In one sibling, recombination occurred between the HLA-A locus and the HLA-B locus. In the second sibling recombination occurred between the HLA-B locus and the HLA-D locus. Strong CML activity was generated in mixed lymphocyte cultures (MLC) when stimulator and responder cells differed in HLA-A, B, and D antigens. MLC involving HLA-D differences alone did not generate CML. Weak, but definite CML activity was generated during MLC with cells differing at HLA-A and HLA-B but sharing HLA-D. HLA-B antigens were good targets for lysis in all combinations studied. HLA-A antigens were poor targets in some but not in all combinations. However, combinations where HLA-A antigens seemed to be good targets could have involved HLA-B differences due to polymorphism of HLA-B7 antigens each inherited from a different parent. HLA-D antigens did not serve as targets for lysis. In three cell experiments, excellent CML activity was generated when responder cells were stimulated by HLA-D antigens and by HLA-A and B antigens present on separate stimulator cells.

Adult↗
PubMed1977

Familial CRST syndrome with sicca complex.

Two patients, a mother and daughter, each with the CRST syndrome, developed Sjögren's syndrome. Both patients had mitochondrial antibodies, smooth muscle antibodies, and a raised serum IgM without clinical evidence of liver disease. This family constitutes the first record of the familial coexistence of the CRST syndrome with Sjögren's syndrome, and the second evidence of vertical inheritance of scleroderma. It is suggested that patients with the CRST syndrome be studied for Sjögren's syndrome and for autoimmune liver disease.

Adult↗
PubMed1976

Skin lesions, angioedema, eosinophilia, and hypocomplementemia.

A six-year-old girl with recurrent urticaria and angioedema, vasculitis, and probable renal disease exhibited marked blood eosinophilia, increased levels of serum IgE, circulating Clq precipitins, and hypocomplementemia with evidence of activation of complement by the classic pathway. Biopsies of skin and muscle revealed heavy infiltrations of the vessel walls with eosinophils. Immunofluorescence studies revealed deposition of IgM, IgE, and C3 in the vessel walls. Exacerbations of the disease were associated with an increase in the eosinophil count and a decrease in the serum levels of C4 and C3. Remission was achieved with corticosteroid therapy. This patient has many features in common with the syndrome of skin lesions, angioedema, and hypocomplementemia recently described in adults.

Child↗
PubMed1976

Immunologic reconstitution in severe combined immunodeficiency following transplantation with parental bone marrow.

A 9-month-old girl with severe combined immunodeficiency was transplanted with BM cells from her father. The child had complete restoration of cell-mediated immune functions. Humoral immune functions remain absent nine months after transplant. Child and father were HL-A identical and their lymphocytes were nonreactive in mixed lymphocyte culture. The parents of the child were first cousins and shared an HL-A haplotype. In countries like Lebanon, where there is a high incidence of first-cousin marriages (15%) and where villages are relatively isolated, the search for histocompatible graft donors should extend beyond the siblings to other members of the family.

B-Lymphocytes↗
PubMed1975

Cooperation between human thymus-derived and bone marrow-derived lymphocytes in the antibody response to ragweed antigen E in vitro.

Human T lymphocytes from patients with ragweed hay fever, when exposed to ragweed antigen E (AgE) in vitro, produced an activity that, in the presence of antigen, induced B cells from AgE-sensitive donors to synthesize and secrete IgE and IgG antibodies to AgE. Anti-AgE specificity was assessed both in vitro and in vivo. B lymphocytes from ragweed-sensitive individuals exposed in vitro to AgE alone failed to transform or to secrete antibody to AgE. The T cells activity had no effect on B cells of individuals not sensitive to AgE. The results of this study suggest that the human reaginic antibody response requires T and B cell cooperation. The experimental approach used may be a useful model for the investigation of the antibody responses of allergic individuals.

Adult↗
PubMed1975

Assessment of the B-lymphocyte population in agammaglobulinemia.

The population of B lymphocytes was assessed in the blood of 16 patients with agammaglobulinemia using immunofluorescence and EAC1423 reactivity as B-cell markers. Lymphocytes were fractionated on gradients of bovine serum albumin which are capable of separating lymphocytes into B-cell-rich and T-cell-rich populations. There was complete absence of B lymphocytes in the majority of patients with X-linked agammaglobulinemia. Normal or increased numbers of B lymphocytes were found in all patients with common variable agammaglobulinemia.

Adolescent↗